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The Clinical Study Of Three-dimensional Reconstruction Of Liver And Tumor In Children And The Mechanism Of Neuroblast Chemotherapy Sensitivity

Posted on:2020-11-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:X J ZhouFull Text:PDF
GTID:1364330590485620Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
Objective Accurate understanding of liver anatomy is critical for safe operation of liver resection and other procedures,the initial liver segmentation study was based on a cadaveric liver perfusion model is inevitable.With the development of digital medical technology and 3D imaging research,through the three-dimensional reconstruction of the digital liver model,the anatomical relationship of the portal vein and hepatic vein in the liver and the vascular variation can be observed from different angles,making it possible to evaluate the individual liver segment and sub-segment in vivo.To segment the liver according to the large amount of three-dimensional(3D)reconstructive images of normal human livers and the vascular system,and based on the anatomic features of the intrahepatic portal veins of the basic functional liver unit required for accurate liver surgery.Methods The CT images of the upper abdomen of 16 hospitals in China,including the Affiliated Hospital of Qingdao University,the Pediatric Hospital of Fudan University,and the Children’s Hospital of Zhejiang University,were collected from October 2013 to March 2017.The enhanced CT primitive DICOM files of 1,260 normal human livers from different age groups were analyzed using the computer-aided surgery system(CAS,Hisense).The 3D liver and liver vascular system were reconstructed,and the digital liver3D model was established.The vascular morphology,anatomical features,and anatomical distributions of intrahepatic portal veins were statistically analyzed.Results The digital liver model obtained from the 3D reconstruction of CAS(Hisense)displayed clear intrahepatic portal vein vessels of level four.Perform a digital liver segments study based on the analysis of level four vascular distribution areas.As the less anatomical variation of left hepatic portal vein,we classified the livers into four types of liver segmentation mainly based on right hepatic portal vein.Type A is similar to Couinaud or Cho’s segmentation,containing 8 segments(537 cases,42.62%).Type B contains 9 segments as there are three ramifications of right-anterior portal vein(464cases,36.82%).The main difference for Type C is the variation of right-posterior portal vein which is sector shape(102 cases,8.10%).Type D contains the cases with special portal vein variations,which needs three-dimensional simulation to design individualized liver resection plan(157 cases,12.46%).These results show that there was no significant difference in liver segmental typing between genders(X~2=2.179,P=0.536)and did not reveal any significant difference in liver segmental typing among the different age groups(X~2=0.357,P=0.949).Conclusion The 3D digital liver model can demonstrate the true 3D anatomical structures,and its spatial vascular variations.The observation of anatomic features,distribution areas of intrahepatic portal veins and individualized liver segmentation achieved via digital medical 3D visualization technology is of great value for understand the complexity of liver anatomy and to guide the precise hepatectomy.Objective Hepatoblastoma is the most common hepatic malignancy in children,accounting for 50% to 60% of children’s primary liver tumors.It occurs within 5 years of age,and the pathogenesis is still unclear.Pediatric hepatoblastoma is usually a large and complex tumor with limited surgical field.In addition,due to the small size of the fine blood vessels and organs in the liver of children and the poor endurance of surgical attack,pediatric hepatoblastoma surgery needs to be more accurate and minimally invasive.The purpose of this study was to explore the clinical application value of computer assisted surgery system(Hisense CAS)in the preoperative resection evaluation and surgical planning of hepatoblastoma in children.Methods 25 children with hepatoblastoma who underwent liver tumor resection from January 2015 to September 2018,Affiliated Hospital of Qingdao University.Preoperative resection was evaluated based on two-dimensional CT and digital liver reconstruction model,and tumor resection rate was compared.Computer-assisted surgical system was applied to guide tumor resection.The preoperative liver function of 25 children with alpha-fetoprotein,operative time,blood loss,postoperative hospitalization days,pathological types and complications were analyzed.Results In 25 cases of hepatoblastoma,only 7 cases could be resected by one-stage operation according to two-dimensional CT.Preoperative evaluation of digital liver model showed that 12 cases could be resected by one-stage operation,and 13 cases suggested delayed operation after chemotherapy.Among them,3 children had huge tumors and poor basic condition,and 1 family member refused to accept chemotherapy.The residual liver volume could be compensated by computer-assisted surgery system,and then one-stage resection was performed.Among 25 children,16 underwent primary resection and 9 delayed resection after chemotherapy.The operation time was 160.6 min(85 min-220 min),the intraoperative bleeding volume was 27.12 ml(3 ml-150 ml),the hospital stay was 10.24 days(5d-15 d),the blood transfusion rate was 28%(7/25).Pathological results confirmed that all patients were hepatoblastoma.All the 25 patients underwent surgical resection of the tumor,and were discharged from the hospital.All patients were followed up.Except for 2 cases of intrahepatic or pulmonary metastases,the other children had no abnormalities.Conclusion The digital liver model obtained by three-dimensional reconstruction of the computer-assisted surgery system is based on omnidirectional observation of the adjacent relationship between the tumor and the blood vessel,virtual surgery design of the surgical plan and calculation of information such as functional residual liver volume that cannot be obtained by two-dimensional CT.Successfully performed surgery on children who were considered unresectable based on 2D CT planning surgery,The resectability rate of the tumors was improved,and the optimal surgical scheme was designed and planned to make the hepatectomy safer.Objective Neuroblastoma is the most common malignancy in children and poses a serious threat to the lives of children.Chemotherapy plays an important role in the treatment of neuroblastoma,but many children are clinically unconscious of chemotherapy.To investigate the effect of miR-142-3p on CDDP resistance of neuroblastoma cells by targeting HMGB1.Methods First,Construct CDDP resistance neuroblastoma cell line SH-SY5Y/CDDP and test the expression level of miR-142-3p by real-time PCR.Second,Detect apoptosis level and IC50 value of SH-SY5Y/CDDP by CCK8 and Elisa after transfection of miR-142-3pmimic.Third,Clone 3’UTR of HMGB1 into luciferase reporter vector to verify that miR-142-3p can target HMGB1.Fourth,test the expression level of HMGB1 in SH-SY5 Y cell after transfection of the miRNA-142-3p mimic by western blot.Finally,detect the IC50 value and apoptosis level of SH-SY5Y/CDDP cells after knockdown of HMGB1 in SH-SY5Y/CDDP cell line by si RNA.Results: First,We contruct the CDDP-resistance cell line SH-SY5Y/CDDP successfully,and the IC50 value of SH-SY5Y/CDDP increased from(4.57±0.65)ug/ml to(23.53±3.87)ug/ml,5.15 times higher than the parents cell line SH-SY5Y;And the expression level of miR-142-3p in SH-SY5Y/CDDP cell decreased remarkably than SH-SY5 Y cell.Second,The apoptosis level of SH-SY5Y/CDDP increased and IC50 value of CDDP decreased(7.02±1.38 VS 24.27±4.13)ug/ml when miR-142-3p expression was upregulated.Third,Mi R-142-3p can inhibit theenzymatic activity of luciferase reporter vector of HMGB1.Fourth,The expression level of HMGB1 decreased when overexpression miR-142-3p in SH-SY5 Y cells.and the expression level of HMGB1 and miR-142-3p was negatively correlated in SH-SY5 Y cell line.Fifth,the apoptosis level of SH-SY5Y/CDDP increased and IC50 value of CDDP decreased from(24.61±4.07)ug/ml,to(9.65±1.39)ug/ml and(8.43±1.76)ug/ml respectively after knockdown of HMGB1 by two si RNA in SH-SY5Y/CDDP cell line.Conclusion The target gene of miR-142-3p is HMGB1,miR-142-3p can increase CDDP resistance of neuroblastoma cell by targeting HMGB1.
Keywords/Search Tags:Hepatic anatomy, Portal vein, Anatomic hepatectomy, Imaging,three-dimensional, Hepatectomy, Surgery, computer-assisted, three-dimensional, neuroblastoma, chemotherapy, miR-142-3p, HMGB1
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